Obstetrics and Gynaecology - Research Publications
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ItemPublic and/or private health care: tuberculosis patients' perspectives in Myanmar.(Springer Science and Business Media LLC, 2009-07-28)BACKGROUND: Tuberculosis is a major public health problem in Myanmar as in other developing countries. About 73% of TB patients seek care at private general practitioners' clinics before presenting to the public TB centre, raising questions about how best to prevent transmission and maintain treatment regimens. METHOD: The study was conducted in two townships in Yangon Division in Myanmar in 2004, and examined treatment seeking behaviour of TB patients and their views towards public and private health care services. This was an exploratory descriptive study. Both quantitative and qualitative research methods were employed in data collection from TB patients, health care professionals, and members of various agencies involved in TB Control Programme. RESULTS: A considerable delay was found between the onset of symptoms of TB and seeking treatment (five days - two months). General practitioners were the first point of contact in all cases. Old TB patients influenced the treatment seeking behaviour and choice of treatment clinics of new TB patients. Most patients viewed the public health sector as a place to obtain free treatment and the private sector as a fee-paying, convenient and better place to seek treatment. CONCLUSION: The involvement of private general practitioners is crucial for effective TB control in Myanmar. The selection of GPs for partnership with the public sector is vital to the success of public-private partnership in controlling TB.
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ItemHealth professionals' advice for breastfeeding problems: not good enough!(Springer Science and Business Media LLC, 2008-09-11)Jane Scott and colleagues have recently published a paper in the International Breastfeeding Journal showing that health professionals are still giving harmful advice to women with mastitis. We see the management of mastitis as an illustration of health professionals' management of wider breastfeeding issues. If health professionals don't know how to manage this common problem, how can they be expected to manage less common conditions such as a breast abscess or nipple/breast candidiasis? There is an urgent need for more clinical research into breastfeeding problems and to improve the education of health professionals to enable them to promote breastfeeding and support breastfeeding women.
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ItemVaginal surgery for pelvic organ prolapse using mesh and a vaginal support device(WILEY, 2008-02)OBJECTIVES: To describe a new surgical procedure for pelvic organ prolapse using mesh and a vaginal support device (VSD) and to report the results of surgery. DESIGN: A prospective observational study. SETTING: Two tertiary referral Urogynaecology practices. POPULATION: Ninety-five women with International Continence Society pelvic organ prolapse quantification stage 2 or more pelvic organ prolapse who underwent vaginal surgery using mesh augmentation and a VSD. METHODS: Surgery involved a vaginal approach with mesh reinforcement and placement of a VSD for 4 weeks. At 6 and 12 months, women were examined for prolapse recurrence, and visual analogue scales for satisfaction were completed. Women completed quality-of-life (QOL) questionnaires preoperatively and at 6 and 12 months. MAIN OUTCOME MEASURES: Objective success of surgery at 6 and 12 months following surgery. Secondary outcomes were subjective success, complications, QOL outcomes and patients' satisfaction. RESULTS: Objective success rate was 92 and 85% at 6 and 12 months, respectively. Subjective success rate was 91 and 87% at 6 and 12 months, respectively. New prolapse in nonrepaired compartments accounted for 7 of 12 (58%) failures at 12 months. Two of 4 mesh exposures required surgery. Sexual dysfunction was reported by 58% of sexually active women preoperatively and 23% at 12 months. QOL scores significantly improved at 12 months compared with baseline (P < 0.0001). CONCLUSION: Vaginal surgery using mesh and a VSD is an effective procedure for pelvic organ prolapse. However, further studies are required to establish the role of the surgery described in this study.
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ItemNo Preview AvailableRole of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence(DOVE MEDICAL PRESS LTD, 2008)Estrogen-containing hormone therapy (HT) is the most widely prescribed and well-established treatment for menopausal symptoms. High quality evidence confirms that estrogen effectively treats hot flushes, night sweats and vaginal dryness. Progestins are combined with estrogen to prevent endometrial hyperplasia and are sometimes used alone for hot flushes, but are less effective than estrogen for this purpose. Data are conflicting regarding the role of androgens for improving libido and well-being. The synthetic steroid tibolone is widely used in Europe and Australasia and effectively treats hot flushes and vaginal dryness. Tibolone may improve libido more effectively than estrogen containing HT in some women. We summarize the data from studies addressing the efficacy, benefits, and risks of androgens, progestins and tibolone in the treatment of menopausal symptoms.
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ItemValidating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium(NATURE PUBLISHING GROUP, 2009-01-22)The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.
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ItemAn immunohistochemical perspective of PPARβ and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours(NATURE PUBLISHING GROUP, 2008-04-22)Peroxisome proliferator-activated receptor beta (PPAR beta) is a member of the nuclear hormone receptor family and is a ligand-activated transcription factor with few known molecular targets including 3-phosphoinositide-dependent protein kinase 1(PDK1). In view of the association of PPAR beta and PDK1 with cancer, we have examined the expression of PPAR beta and PDK1 in normal ovaries and different histological grades of ovarian tumours. Normal ovaries, benign, borderline, grades 1, 2 and 3 ovarian tumours of serous, muciuous, endometrioid, clear cell and mixed subtypes were analysed by immunohistochemistry for PPAR beta and PDK1 expression. All normal ovarian tissues, benign, borderline and grade 1 tumours showed PPAR beta staining localised in the epithelium and stroma. Staining was predominantly nuclear, but some degree of cytoplasmic staining was also evident. Approximately 20% of grades 2 and 3 tumours lacked PPAR beta staining, whereas the rest displayed some degree of nuclear and cytoplasmic staining of the scattered epithelium and stroma. The extent of epithelial and stromal PPAR beta staining was significantly different among the normal and the histological grades of tumours (chi(2)=59.25, d.f.=25, P<0.001; chi(2)=64.48, d.f.=25, P<0.001). Significantly different staining of PPAR beta was observed in the epithelium and stroma of benign and borderline tumours compared with grades 1, 2 and 3 tumours (chi(2)=11.28, d.f.=4, P<0.05; chi(2)=16.15, d.f.=4, P<0.005). In contrast, PDK1 immunostaining was absent in 9 out of 10 normal ovaries. Weak staining for PDK1 was observed in one normal ovary and 40% of benign ovarian tumours. All borderline and malignant ovarian tumours showed positive cytoplasmic and membrane PDK1 staining. Staining of PDK1 was confined to the epithelium and the blood vessels, and no apparent staining of the stroma was evident. Significantly different PDK1 staining was observed between the benign/borderline and malignant ovarian tumours (chi(2)=22.45, d.f.=5, P<0.001). In some borderline and high-grade tumours, staining of the reactive stroma was also evident. Our results suggest that unlike the colon, the endometrial, head and neck carcinomas, overexpression of PPAR beta does not occur in ovarian tumours. However, overexpression of PDK1 was evident in borderline and low- to high-grade ovarian tumours and is consistent with its known role in tumorigenesis.
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ItemPriorities for Endometriosis Research: Recommendations From an International Consensus Workshop(SAGE PUBLICATIONS INC, 2009-04)Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.
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ItemImproving the outcome of infants born at <30 weeks' gestation - a randomized controlled trial of preventative care at home(BMC, 2009-12-03)BACKGROUND: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems. METHODS/DESIGN: We have designed a randomized controlled trial to assess the effectiveness of a preventative care program delivered at home over the first 12 months of life for infants born very preterm (<30 weeks of gestational age) and their families, compared with standard medical follow-up. The aim of the program, delivered over nine sessions by a team comprising a physiotherapist and psychologist, is to improve infant development (cognitive, motor and language), behavioral regulation, caregiver-child interactions and caregiver mental health at 24 months' corrected age. The infants will be stratified by severity of brain white matter injury (assessed by magnetic resonance imaging) at term equivalent age, and then randomized. At 12 months' corrected age interim outcome measures will include motor development assessed using the Alberta Infant Motor Scale and the Neurological Sensory Motor Developmental Assessment. Caregivers will also complete a questionnaire at this time to obtain information on behavior, parenting, caregiver mental health, and social support. The primary outcomes are at 24 months' corrected age and include cognitive, motor and language development assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III). Secondary outcomes at 24 months include caregiver-child interaction measured using an observational task, and infant behavior, parenting, caregiver mental health and social support measured via standardized parental questionnaires. DISCUSSION: This paper presents the background, study design and protocol for a randomized controlled trial in very preterm infants utilizing a preventative care program in the first year after discharge home designed to improve cognitive, motor and behavioral outcomes of very preterm children and caregiver mental health at two-years' corrected age. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12605000492651.
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ItemLeukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of tissue inhibitor of metalloproteinases-1 and -2(OXFORD UNIV PRESS, 2008-08)BACKGROUND: Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that is essential for blastocyst implantation in mice. It has been suggested that LIF may play a role in human first trimester extravillous trophoblast (EVT) invasion. The aim of the present study was to establish whether LIF induces changes in EVT function related to invasiveness. METHODS: Primary first trimester human EVT cell cultures were treated with/without LIF and the effects on cell adhesion to fibronectin (FN), vitronectin (VN) and laminin (LN) were assessed. Transcript levels of integrin subunits that mediate cell adhesion to these extracellular matrix (ECM) elements were determined by real-time RT-PCR. Matrix metalloproteinase (MMP)2 and MMP9 secretion was assessed by gelatine zymography and tissue inhibitors matrix metalloproteinase (TIMP) -1 and TIMP-2 secretion by enzyme-linked immunosorbent assay. RESULTS: EVT cells showed increased adhesion to FN, VN and LN ECM elements in response to LIF (20, 20 and 29%, respectively, P < 0.05 FN and VN compared to control; and P < 0.001 LN compared to control). Integrin beta(4) mRNA levels decreased by 50% following LIF treatment (P < 0.001 versus control). MMP2 and MMP9 secretion was not affected by LIF but LIF did increase secretion of TIMP-1 and -2 (P < 0.001 versus control). LIF stimulated the phosphorylation of signal transducer and activator of transcription (STAT) 3 protein while it did not affect STAT3 protein abundance. The addition of a LIF inhibitor attenuated the LIF-induced STAT3 phosphorylation in EVT. CONCLUSION: The results suggest that LIF can regulate EVT invasion, suggesting an important role in early placental development.
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ItemA distinct cohort of the TGFβ superfamily members expressed in human endometrium regulate decidualization(OXFORD UNIV PRESS, 2008-06)BACKGROUND: Successful blastocyst implantation requires the differentiation of human endometrial stromal cells (HESC), a process known as decidualization. Activin A, a transforming growth factor beta (TGFbeta) superfamily member, enhances HESC decidualization and localizes to decidual cells in human endometrium. Other TGFbeta superfamily members, including BMP2, BMP4, BMP7, GDF5, GDF8, GDF11, TGFbetas and Nodal, may also play a role during decidualization. This study aimed to identify these TGFbeta family members in human endometrium, and to determine whether they are involved in human decidualization. METHODS: Protein localization of TGFbeta family members was examined in secretory phase human endometrium and first trimester decidua by immunohistochemistry. mRNA expression was examined in HESC. Activin inhibitors (Activin-M108A/SB431542) with differing specificities for the other TGFbeta members under consideration were applied during HESC decidualization in vitro. The secretion levels of potential TGFbeta superfamily members were measured during decidualization, and recombinant proteins added to examine their effect. RESULTS: This study has identified BMP2, BMP4, BMP7, GDF5, GDF8 and GDF11 but not Nodal in secretory phase human endometrium, but only BMP2, GDF5 and TGFbeta1 protein were detected in decidual cells. All ligands except Nodal were expressed by cultured HESC. Both inhibitors significantly reduced decidualization validating the role of activin, but potentially also other TGFbeta members, during decidualization. BMP2 and TGFbeta1 secretion increased during HESC decidualisation and exogenous administration of these proteins significantly enhanced decidualization in vitro. CONCLUSIONS: Like activin, BMP2 and TGFbeta1 are likely to be involved in HESC decidualization. This is the first study to identify and localize BMP4, BMP7, GDF5, GDF8 and GDF11 in secretory phase human endometrium. Understanding the factors critical for the implantation process is needed for improving fertility and pregnancy outcomes.